Repeated limited access to IV cocaine self-administration: conditioned autonomic rhythmicity illustrating ”predictive homeostasis”

Abstract 

Rationale: Regular cocaine self-administration may act as a ”Zeitgeber” in animals and humans, and physiological rhythms may peak at the time when the drug is usually self-administered. Objective: To investigate whether or not daily sessions of cocaine self-administration for 2 weeks would synchronize autonomic rhythms to the time of daily access. Methods: Two weeks after implant of a jugular catheter and telemetry sender, each rat’s heart-rate (HR) and core temperature (Tc) rhythms were well entrained to the 12:12-h light:dark cycle (lights off: 0900 hours). For the next 2 weeks rats self-administered cocaine during daily sessions at 1300 hours. The circadian and ultradian oscillations of HR and Tc recorded during the 3 days after the last self-administration (SA) session were quantified by multi-oscillator cosinor analysis. Results: The HR and Tc were elevated during the initial 0.25 mg cocaine infusions of the daily session. This initial tachycardia disappeared as cocaine continued to be self-administered in accumulating amounts, while the locomotor activity remained elevated. After the last SA session the peak (acrophase) of the two cycles/day component in HR and Tc rhythms aligned to the time of day when cocaine self-administration had previously been scheduled. The amplitude of the circadian and ultradian HR and Tc oscillations as well as their circadian acrophase were not impacted by repeated daily time-limited cocaine self-administration. Conclusions: Cocaine controls the behavior and autonomic functions of rats self-administering limited amounts of cocaine during regular daily sessions, and this controlling influence extends beyond the last daily access period.